Showing posts with label Toxicology. Show all posts
Showing posts with label Toxicology. Show all posts

Monday, January 1, 2018

Benzodiazepine Overdose

Benzodiazepines work through GABAa receptors and this class of medications are commonly used in Emergency Department to aid sedation, anxiolysis and amnesia. IV administration may result in significant complications, particularly respiratory depression and hypotension, especially when combined with opioids or other sedatives.


Alternatively, BZDs are also used as first line anticonvulsants. Patients with mental health issues are often given this set of medications to treat concomitant anxiety and thus overdose is frequently a problem. Fortunately, isolated benzodiazepine overdose has low mortality and fatalities are rare. In cases of mixed overdose i.e combination with TCAs and opioids, complication rates are higher. Out-patients use of BZDs is limited to short-term treatment of anxiety and insomnia.




Clinical Presentation (think EtOH intoxication)
  • Typical - Slurred speech, Drowsiness, Stuporous, Confusion, Ataxia, Incoordination and Coma
  • Paradoxical reactions - Excitement, Anxiety, Aggression and delirium are more commonly seen in hyperactive children and psychiatric patients


Treatment
  • Maintain ABCs
  • Use Flumazenil if no contra-indications 
  • Wait for the drug to wear off

Consider activated charcoal in case of early presentations and have a secured airway prior to that. It is debatable to intubate someone with a BZD overdose coming with a low GCS (say E1M5V1) with isolated BZD overdose. Make a decision in liaison with ITU team as there is a clear and reversible cause of low GCS. However, this needs to weighed against risk of aspiration if the patient vomits. 

Flumazenil is a selective antagonist of the central effects of benzodiazepines. It should be used only in two scenarios:
  • Definite isolated BZD overdose in naive BZD user
  • Reversal of iatrogenic benzodiazepine induced sedation (see contra-indications below)
Recurrent benzodiazepine toxicity may result once the effects of flumazenil have worn off.  Flumazenil Dose: 0.2 milligram IV q1min up to a total dose of 3 milligrams

Contraindications to Flumazenil:
  • Chronic BZD users
  • Mixed Overdoses (esp TCA)
  • Seizure Disorder
  • Suspected raised ICP
Flumazenil induced seizures should be treated with other GABAA receptor agonists (propofol and phenobarbitone) because the benzodiazepine site on the receptor is antagonised. 


Admit if:
  • Persistent drowsiness
  • Respiratory depression
  • Hypotension

Take Home:
  • Definite indication of Flumazenil is iatrogenic overdose of BZD
  • Mortality is low with isolated BZd overdose --> Maintains ABCs and wait for the drug to wear off
  • Reduce dose to half when sedation elderly 

References:


  1. Ngo AS, Anthony CR, Samuel M, Wong E, Ponampalan R: Should a benzodiazepine antagonist be used in unconscious patients presenting to the emergency department? Resuscitation 74: 27, 2007. 
  2. Charlson F, Degenhardt L, McLaren J, et al: A systematic review of research examining benzodiazepine-related mortality. Pharmacoepidemiol Drug Saf 18: 93, 2009

Posted by:

              
     Lakshay Chanana
     
     Speciality Doctor
     Northwick Park Hospital
     Department of Emergency Medicine
     England

     @EMDidactic


  
  

Monday, October 2, 2017

Alcohol Withdrawal in ED

Alcohol withdrawal is seen in those who stop or cut down their drinking abruptly. Symptoms  of withdrawal include tremors, nausea and vomiting, diaphoresis, hyperdynamic vitals, fever, agitation, craving, and anxiety, seizures, hallucinations, and delirium. Symptoms may begin within few hours after reduction in alcohol consumption. 

ED management
Ruling out the co-existing diagnosis and mimics (hyponatremia, hypoglycemia, hypomagnesemia, DKA, Wernicke’s encephalopathy, toxic ingestions, primary seizures, head injury, infection, sepsis)


Alcohol withdrawal seizures are tonic-clonic seizures that occur 6-48 hours after the decrease in intake or the last drink. Alcohol withdrawal seizures remains a diagnosis of exclusion. Focal seizures should prompt search for another diagnosis. Benzodiazepines are the drugs of choice for EtOH withdrawal fits. Phenytoin should not be used unless there is an underlying structural lesion. Lorazepam is typically started at 2mg IV and repeated as needed. 



Delirium tremens is characterised by fluctuating disturbances in consciousness, confusion, agitation, inattention and impairment in cognition and hallucinations. Patients are at risk of fluid and metabolic imbalances. High doses of sedatives are required to control agitation. Benzodiazepines are the initial treatment of choice and those who do not respond to BZDs need phenobarbital, propofol, or haloperidol. However, antipsychotics should be given only after adequate benzodiazepines are administered.

Treatment of concomitant illnesses and providing supportive care (hydration and electrolyte imbalance) is an important part of management. Patients may also need physical restraints until they are quiet and Pabrinex and Mg should be considered for all.


Goals of therapy

Our goal is to reduce autonomic hyperactivity and agitation. This is achieved mainly through BZDs.  

Lorazepam 1mg = Midazolam 2mg = Diazepam 5mg = Chlordiazepoxide 25mg

Lorazepam is well tolerated by patients with advanced liver disease. Clinical Institute Withdrawal Assessment for Alcohol–Revised (CIWA) is a validated (not validated specifically for ED use), structured instrument for guiding continuing treatment once a diagnosis of alcohol withdrawal is established. A score <8 represents mild withdrawal; score of 9 to 15 moderate withdrawal, and score >15 severe withdrawal. 


Admission Criteria
  • Concomitant other diagnosis 
  • Suicidal or homicidal ideation 
  • Advanced age
  • Not responding well to ED treatment
  • Prior history of delirium tremens 
  • Alcohol withdrawal seizures


References:
  1. Rathlev NK, Ulrich AS, Delanty N, D’Onofrio G: Alcohol-related seizures. J Emerg Med 31: 157, 2006.
  2. Greenberg DM, Lee JW: Psychotic manifestations of alcoholism. Curr Psychiatry Rep 3: 314, 2001.
  3. Kahan M, Borgundvaag B, Midmer D: Treatment variability and out come differences in emergency department management of alcohol withdrawal. Can J Emerg Med 7: 87, 2005.
  4. Clinical Institute Withdrawal Assessment for Alcohol scale. CIWA-Ar available at: http://www.stvincentshospital.ie/documents/CIWA-Ar.pdf. Accessed February 22, 2010.
  5. D’Onofrio G, Rathlev NK, Ulrich AS, et al: Lorazepam for the prevention of recurrent seizures related to alcohol. N Engl J Med 340: 915, 1999.
  6. McCowan C, Marik P: Refractory delirium tremens treated with propofol: a case series. Crit Care Med 28: 1781, 2000.
  7. Kang TM: Propofol infusion syndrome in critically ill patients. Ann Pharmacother 36(9): 1453, 2002.
  8. Mayo-Smith MF, Beecher LH, Fischer TL, et al; for the Working Group on the Man- agement of Alcohol Withdrawal Delirium, Practice Guidelines Committee, American Society of Addiction Medicine: Management of alcohol withdrawal delirium: an evi- dence-based practice guideline. Arch Intern Med 164: 1405, 2004.
  9. Kosten TR, O’Connor PG: Management of drug and alcohol withdrawal. N Engl J Med 348: 1786, 2003. 

Posted by:

              
     Lakshay Chanana
     
     Speciality Doctor
     Northwick Park Hospital
     Department of Emergency Medicine
     England

     @EMDidactic



Monday, September 25, 2017

Cocaine Toxicity

Cocaine is one of the most commonly used recreational drug. It is both a CNS stimulant and a local anaesthetic.Its clinical effects and toxicity are due to sympathetic nervous system stimulation. Cocaine can be used topically, swallowed, or injected IV. 


                          


Cocaine is metabolized by plasma cholinesterase. Therefore, deficiency of this enzyme may predispose affected patients to life-threatening toxicity.  Central effects of cocaine are mediated by enhancement of excitatory amino acids and blockade of presynaptic reuptake of norepinephrine, dopamine, and serotonin. The excess of neurotransmitters at postsynaptic receptor sites leads to sympathetic activation, producing a characteristic toxidrome of mydriasis, tachycardia, hypertension, and diaphoresis, dysrhythmias, seizures, and hyperthermia. 

Like other local anesthetics, cocaine also inhibits conduction of nerve impulses by blocking fast sodium channels in the cell membrane. This can lead to QRS widening and QT-interval prolongation. 

Systemic Effects
Cardiac
  • Dysrhythmias (Na/K Channel Blockade - Sinus Tachy, Wide QRS, Prolonged QTc, Rightward Axis, Brugada Pattern, Takotsubo Cardiomyopathy)
  • Myocarditis
  • Acute coronary syndromes
  • Aortic rupture and aortic/coronary artery dissection
  • Cocaine-induced chest pain (Coronary Vasospasm, also hastens atherogenesis through increased platelet aggregation, thrombogenesis)
CNS
  • Seizures
  • Stroke (ischemic and haemorrhages)
  • Hypertension
  • Spinal cord infarction
  • Cerebral vasculitis
  • Intracranial abscesses
  • Crack dancingChoreoathetosis and repetitive movements due to dopamine dysregulation. 
  • Blindness (central retinal artery occlusion)

Other effects
  • Pulmonary haemorrhage
  • Pneumonitis, Asthma
  • Pulmonary edema
  • Acute Lung Injury
  • Thermal uvulitis 
  • Bowel schema and necrosis
  • Splenic infarctions
  • Rhabdomyolysis and AKI 
  • Renal infarction 

Differential Diagnosis of Sympathomimetic Syndrome
  • Anticholinergic Syndrome
  • Serotonin Syndrome
  • Neuroleptic Malignant Syndrome
  • Alcohol Withdrawal
  • Sepsis and CNS Infections
  • Hypoglycaemia, Metabolic (Electrolyte Issues)
  • Thyrotoxicosis
  • Pheochromocytoma
  • Psychosis
  • Heat Stroke 

Management
  • Benzodiazepines are the drugs of choice for sedation
  • Antipsychotics increase QT prolongation and increase risk of ventricular dysrhythmias
  • Treat Cardiac Chest Pain with aspirin and nitroglycerin, CCBs and reperfusion therapy if needed.  
  • Use of β-adrenergic antagonists (“β-blockers”) in the management of cocaine-associated myocardial ischemia or infarction is controversial. 
  • Sinus tachycardia - Rx with sedation, cooling, and intravenous fluid rehydration 
  • Reentrant supra ventricular tachycardia /Fast atrial fibrillation or flutter - Rx with CCBs
  • Wide-complex tachycardia - Rx with sodium bicarbonate (do not alkalinize above a pH of 7.55). Although Lidocaine is also a Na Channel blocker, it may be considered for use in refractory arrhythmias.
  • Torsades de points - Rx with Magnesium, lidocaine, and overdrive pacing.
  • Hypotension/Persistent Arrhythmias - Intravenous lipid emulsion should be considered in this scenario.
  • Severe hypertension - Rx with sedation or GTN drip or Phentolamine
  • Rhabdomyolysis - IV Fluids
  • Seizures - BZD, Phenobarbitone (Do not Rx with phenytoin which may worsen Na Channel Blockade)

References:
  1. Zimmerman JL: Cocaine intoxication. Crit Care Clin 28: 517, 2012. 
  2. Phillips K, Luk A, Soor GS, Abraham JR, Leong S, Butany J: Cocaine cardiotoxicity: a
  3. review of the pathophysiology, pathology, and treatment options. Am J Cardiovasc Drugs 9: 177, 2009. 
  4. Lange RA, Cigarroa RG, Yancy CW, et al: Cocaine-induced coronary artery vasocon-striction. N Engl J Med 321: 1557, 1989. 
  5. Hollander JE, Hoffman RS: Cocaine-induced myocardial infarction: an analysis and
  6. review of the literature. J Emerg Med 10: 169, 1992. 
  7. O’Leary ME, Hancox JC: Role of voltage-gated sodium, potassium and calcium channels in the development of cocaine-associated cardiac arrhythmias. Br J Clin Pharmacol 69:427, 2010. 
  8. Yap YG, Behr ER, Camm AJ: Drug-induced Brugada syndrome. Europace 11: 989, 2009.
  9. Arora S, Alfayoumi F, Srinivasan V: Transient left ventricular apical ballooning after cocaine use: is catecholamine cardiotoxicity the pathologic link? Mayo Clin Proc 81: 829, 2006. 
  10. Rangel C, Shu RG, Lazar LD, Vittinghoff E, Hsue PY, Marcus GM: Beta-blockers for chest pain associated with recent cocaine use. Arch Intern Med 170: 874, 2010. 
  11. Jakkala-Saibaba R, Morgan PG, Morton GL: Treatment of cocaine overdose with lipid emulsion. Anaesthesia 66: 1168, 2011. 

Posted by:

              
     Lakshay Chanana
     
     Speciality Doctor
     Northwick Park Hospital
     Department of Emergency Medicine
     England

     @EMDidactic




Monday, September 11, 2017

EtOH intoxication

Ethanol is the one of the most commonly abused drug in the world. Mishaps generally happen due to secondary injuries after intoxication. We all see frequent attenders in ED who visit us almost every weekend and it is easy to miss underlying potentially life-threatening diseases if we fail to follow a systematic way to evaluate them.

Alcohol Metabolism
Ethanol is a CNS depressant that enhances the inhibitory neurotransmitter GABA receptors and blockade of excitatory NMDA receptors. Because of the phenomenon of tolerance, blood ethanol levels correlate poorly with degree of intoxication.  At low concentrations, ethanol metabolism follows first-order kinetics, but as concentrations rise, metabolism switches to zero-order kinetics i.e. a fixed amount is metabolised per unit of time. Rates of elimination from the blood vary between 20-30 milligrams/dL/h.
The legal limit to drive a vehicle varies in different countries. UK, Canada and the United States state 80 mg/dL as the legal definition of intoxication for the purposes of driving motor vehicles whereas in India, the limit is 30mg/dL. 



 Clinical Presentation
Lethargy, Drowsiness, Disinhibition, Euphoria, Agitation and Combativeness are classical clinical features. However, severe intoxication may present with slurred speech, nystagmus, ataxia, and decreased motor coordination and this can be hard to differentiate from Wernicke’s. Treat them with fluids if they are tachycardic (reflex tachycardia due to peripheral vasodilatation). Fever should prompt workup for sepsis and possible Delirium Tremens. Ethanol ingestion may also cause hypoglycemia, due to poor glycogen reserve, poor oral intake and reduced gluconeogenesis.

Potential Mimics and co-existing conditions
  • Encephalopathy (Hepatic, Uremic, Septic)
  • Hypoglycaemia
  • Traumatic Brain Injury (Subdural)
  • Stroke
  • Seizure
  • Wernickes
  • Concomittant drug ingestions
  • Dyselectrolytemia (HypoNa, HyperNa, HyperCa)
  • Alcoholic Ketoacidosis
  • Hypothermia
  • DKA
  • Myxoedema
  • Psychosis
  • Alcoholic Hepatitis and Pancreatitis

ED Management
Performing a detailed physical examination is paramount (Speech, Cranial Nerves, Gait, Nystagmus, GCS, Cerebellum, Evidence of trauma, Abdomen exam) to avoid missing co-existing conditions. Fill the gaps in your history via paramedics, by standers. Usually, uncomplicated intoxication improves within a few hours but if they don’t get sober or worsen then begin evaluation for other causes of altered mental status.
If history and exam are benign then investigations are of limited benefit. At least, obtain a bedside glucose level or a venous blood gas. Acute intoxication may be associated with mild metabolic acidosis, but a significant HAGMA suggests the presence of lactic acidosis, ketoacidosis, or methanol or ethylene glycol toxicity. Ethanol blood levels are not required unless there is a diagnostic dilemma but many prefer to do it anyways to ensure documentation. 
Most physicians agree that observation is the way to go until they are sober. Manage symptoms and beware of hypoglycemia. The classical teaching of Wernicke’s encephalopathy being precipitated by prolonged sustained administration of IV carbohydrate does not hold true and currently there is no evidence that a single dose of IV glucose can cause Wernicke’s.  Otherwise, majority of them do NOT need Pabrinex but administer if you suspect Wernicke’s. Additionally, bolus IV fluids do not help to attain sobriety any earlier. Metadoxine is used in some countries to enhance the metabolism of ethanol and accelerate recovery.
Take Home:
Simple ethanol intoxication needs ED observation until sober. Admit if they are suicidal, homicidal or psychotic. Always try and arrange appropriate transport for them and discharge in the care of a responsible companion.

Posted by:

              
     Lakshay Chanana
     
     Speciality Doctor
     Northwick Park Hospital
     Department of Emergency Medicine
     England

     @EMDidactic




Monday, June 22, 2015

Monday, June 8, 2015

Corrosive Poisoning

Corrosive poisoning is a common emergency as corrosive agents are easily available for household use. Corrosives can injure the GI tract by causing tissue necrosis, perforation, fibrosis, stricture formation and malignancy years after the exposure. These compounds include acids, bases, salts, heavy metals, iodine tincture etc. 




Acids
  • Car battery fluid (sulfuric acid)
  • Descalers (hydrochloric acid)
  • Metal cleaners (nitric acid)
  • Rust removers (hydrogen fluoride) 
Alkalis
  • Bleach (hypochlorite)
  • Sodium hydroxide (liquid lye) 

Pathophysiology
Alkali ingestion: Causes liquefaction necrosis. This process includes protein dissolution, collagen destruction, fat saponification, cell membrane emulsification, submucosal vascular thrombosis and cell death.

Acid ingestion: Causes coagulation necrosis. In this process, hydrogen (H+) ions desiccate epithelial cells producing an eschar. This process leads to edema, erythema, mucosal sloughing, ulceration and necrosis of tissues.

Both acids and alkalis cause fibrosis and stricture formation 



Signs and Symptoms

Clinical presentation varies and depends on the type/quantity of the agent ingested, timing of ingestion, presence of food in the stomach. Burns to the lips, mouth, and oropharyx may be seen but this does not necessarily correlate to the degree of injury tothe esophagus or stomach. Patients with airway deem may present with stridor, aphonia, hoarseness, or dyspnea. Other presenting symptoms include abdominal or chest pain, nausea/vomiting, GI bleed, dysphagia, odynophagia, drooling. 

If there is GI perforation, it may result in fluid loss causing renal failure, altered mental status, lethargy, arrythmias, respiratory distress and seizures.

Investigations
CBP
Basic Metabolic Profile
ABG
CXR (look for free air)
Type and Cross Match 
CT Scan (for suspected perforation despite negative X-Rays and to assess oesophageal wall thickness)
Endoscopy (for direct evaluation and management of strictures)

Esophagogastroduodenoscopy should be performed in the first 12 to 24 hours post-ingestion with great care, to avoid iatrogenic perforation. The grade and extent of the lesions of the upper gastrointestinal tract can be determined and classified according to the Zargar’s modified endoscopic classification of burns due to corrosive ingestion

Grade Description
  1. 0  Normal mucosa
  2. 1  Erythema/Hyperemia
  1. 2a  Superficial ulcer/erosion/friability/hemorrhage/ exudates
  2. 2b  Findings in 2a + deep discrete/circumferential ulcers
  1. 3a  Scattered necrosis (black/grey discoloration)
  2. 3b  Extensive/circumferential necrosis of mucosa 

Severe hypopharyngeal burns are an absolute contraindication for esophagogastroduodenoscopy.

Management 

1. If only a small amount is ingested: Observe and discharge from the ED if tolerating orallly, asymptomatic and normal intra oral examination. 

2. Major Ingestion
  • Pay special attention to the Airway/Oxygenation
  • IV Fluids
  • Add PPIs (reduce exposure of injured esophagus to gastric acid, which may result in decreased stricture formation.)
  • Antibiotics if there is evidence of perforation
  • Don't forget to add pain relief 
  • Keep Nil by Mouth 
Activated charcoal is relatively contraindicated in caustic ingestions because of poor adsorption and endoscopic interference. Emergency surgical intervention is indicated in case of perforation or peritonitis, or if uncontrolled massive hematemesis occurs. 

DO NOT
  • Induce Emesis (risk of mucosal injury and perforation)
  • Insert NG Tube (may cause esophageal perforation and increase the risk of aspiration)
  • Do Lavage (risk of damage to oesophagus and aspiration)
  • Try to neutralise the substance (risk of heat production resulting from this exothermic reaction
  • Administer systemic steroids


Nutrition: Endoscopic grade of lesions needs to be assessed for planning nutritional support in patients with caustic ingestion. Patients with Grade 1/2a lesions on endoscopy can tolerate oral feeds, while those with Grade 2b/3a lesions will need nasoenteral feeding. Patients with Grade 3b lesions require gastrostomy for enteral feeding and rarely need total parenteral nutrition (TPN). 

Acute presentation 
Within 48-72 hours of corrosive ingestion: Upper GI endoscopy should be performed on Day 1-2. (ideally between 12-24 hours of ingestion). If endoscopy reveals only mild lesions, then the patient can be discharged and clinical follow-up should be done at one month. If severe lesions are found on endoscopy, then surgical gastrostomy is indicated, which should be followed by repeat endoscopy and dilatation after three weeks.

Delayed Admission
Within 72 hours to three weeks of corrosive ingestion: No endoscopy is indicated here. Gastrostomy should be done if there is severe dysphagia. Endoscopy and dilatation of stricture (if present) should be done three weeks after ingestion.


Late Admission
More than three weeks of ingestion: Requires endoscopy and dilatation of stricture. If the procedure is successful, then follow-up endoscopy should be done at one month. If the procedure is unsuccessful, then surgical gastrostomy is performed, which is followed by retrograde dilatation of stricture after 10 days of operation.


Complications of the Disease and/or Management
Aspiration of corrosive substances into the respiratory tree may cause endotracheal or bronchial necrosis with mediastinitis. Acute kidney injury, disseminated intravascular coagulation, acid-base disturbances and pneumonia. Oesophageal stricture formation is the most feared long-term complication; stenosis gastric antrum or pylorus may also occur, as may fistula formation.

Stricture formation begins weeks to months after injury and is the most important consequence of corrosive poisoning. Procedures used for prevention and treatment of strictures are:

  1. Dilatation therapy: This is done 3-6 weeks after injury, progressively larger bougies are passed over endoscopically placed guide wires for dilatation. 
  2. Surgery: Esophageal strictures resistant to dilatation therapy may require surgery that includes resection of stricture surgically and esophageal bypass surgery. 
Key Points:
1. Both acids and Alkalis can cause strictures.
2. Endoscopy performed in the first 12 to 24 hours following ingestion is the gold standard  to assess the GI tract.
3. Pay attention to Airway, Hydration, Nutrition.
4. Say no to NG tube, gastric lavage, emetics, dilution and neutralisation, systemic steroids and activated charcoal.


For further reading:


  1. In: Critical Care Toxicology: Diagnosis and Management of the Critically Poisoned Patient. 1st edition, Brent, Wallace, Burkhart, Phillips, Donovan (Eds.) 2005:p. 1035-44.
  2. Caustics. In: Goldfrank’s Toxicologic Emergencies. 8th edition.
  3. Zargar SA, Kochhar R, Mehta S, Mehta SK. The role of fiberoptic endoscopy in the management of corrosive ingestion and modified endoscopic classification of burns. Gastrointest Endosc 1991;37(2):165-9.
  4. Anderson KD, Rouse TM, Randolph JG. A controlled trial of corticosteroids in children with corrosive injury of the esophagus. N Engl J Med 1990;323(10):637-40.
  5. Acids and alkalis. The Poisoning and Toxicology Handbook. 4th edition, Jerrold B. Leikin, Frank P. Paloucek Informa Healthcare, USA 2007:p.713-9.
  6. Alkali injury. In: Clinical Management of Poisoning and Drug Overdose. 3rd edition, Lester M. Haddad, Michael W. Shannon, and James F. Winchester (Eds.) 1998: p.817-20. 
  7. http://medind.nic.in/iaa/t12/i8/iaat12i8p131.pdf